Molecular Genetics of Melanoma

 描述(由申请人提供)：此次K24黑色素瘤分子遗传学续签申请是候选人上一次K24拨款的扩展，通过下一代测序对患者风险预测和快速增长的分子治疗领域进行了更多的科学和指导投资。K24的头五年有助于为候选人提供受保护的时间，以培训以患者为导向的研究人员。他的研究结果导致了第一个黑色素瘤贝叶斯-孟德尔风险预测模型(MelaPRO)，并描述了黑色素瘤倾向家族中新的MITF和BAP1突变。这位候选人指导了19个人，发表了52篇手稿，并成功竞争了超过280万美元的同行评议拨款。自2010年首次获得K24奖以来，大规模并行测序技术已经变得司空见惯，基因组药物正被部署在患者的床边。K24的更新建议利用精确医学的力量来更全面地描述黑色素瘤的风险，并利用新发现的分子驱动因素来改进黑色素瘤的治疗方法。科学扩展建立在候选人在以患者为导向的遗传学研究方面的长期经验基础上，并为他提供了在跨学科研究的新领域指导受训人员的机会。候选人和MGH分析转换遗传学单位/布罗德研究所和MGH癌症中心/亨利和贝琳达·特梅尔中心的研究人员之间已经存在的针对靶向治疗的紧密交织的多学科合作将允许(I)指导和招募无关领域的受训人员进入以患者为导向的研究的新机会，(I)获得患者和患者衍生材料进行分析，(Iii)明确的基础设施，以 开展拟议的研究和(Iv)目前不在候选人投资组合中的新的资金领域。这一奖项还将使候选人能够开发新的专业领域，编纂新的指导方法，并在以患者为导向的研究中采取新的方向。

 DESCRIPTION (provided by applicant): This K24 renewal application for Molecular Genetics of Melanoma is an expansion of the candidate's previous K24 grant with greater scientific and mentorship investment in patient risk prediction through Next Generation sequencing and in the rapidly growing area of molecular therapeutics. The first five years of this K24 was instrumental in providing the candidate protected time to train investigators in patient-oriented research. The results of his research led to the first Bayes-Mendel risk prediction model in melanoma (MelaPRO) and the description of novel MITF and BAP1 mutations in melanoma-prone families. The candidate was able to mentor 19 individuals, publish 52 manuscripts and successfully compete for over $2.8 million in peer-reviewed grants. Since the initial K24 award in 2010, massive parallel sequencing technologies have become commonplace and genomic medicine is being deployed at the patient's bedside. This K24 renewal proposes to exploit the power of precision medicine to more comprehensively profile melanoma risk and to capitalize on newly-discovered molecular drivers to improve melanoma therapeutics. The scientific expansion builds upon the candidate's long-time experience with patient- oriented genetics investigation and affords him the opportunity to mentor trainees in new areas of interdisciplinary research. The tightly-woven multidisciplinary collaborations which already exist between the candidate and investigators at the MGH Analytic Translational Genetics Unit/Broad Institute and the MGH Cancer Center/Henri and Belinda Termeer Center for Targeted Therapies will allow for (i) new opportunities to mentor and recruit trainees in unrelated fields into patient-oriented research, (i) access to patients and patient-derived material for analysis, (iii) well-defined infrastructures to carry out the proposed studies and (iv) new areas of funding not currently in the candidate's portfolio. This award will also enable the candidate to develop new areas of expertise, to codify new approaches to mentorship and to take on new directions in patient-oriented research.